Current Practice for Therapeutic Drug Monitoring of Biopharmaceuticals in Rheumatoid Arthritis

Abstract

The treatment of rheumatoid arthritis (RA) has largely improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes because of the presence of antidrug antibodies (ADAs). In some instances, clinicians may increase or taper the dose depending on the clinical response. Besides the current clinical-based practice, a tailored strategy based on drug monitoring has emerged as a way to improve the use of these drugs. However, the relevance of this therapeutic drug monitoring (TDM) of biopharmaceuticals in RA is still unknown. In this literature review, we examine the most relevant articles dealing with the concentration-response relationship, ADA detection and pharmacokinetics in RA patients receiving biopharmaceuticals. A concentration-response relationship was clearly established for TNF inhibitors. Moreover, ADA positivity was associated with low drug concentrations, poor clinical outcome, and reduced drug survival for TNF-inhibitor monoclonal antibodies. Concomitant use of disease-modifying antirheumatic drugs, especially methotrexate, is associated with good clinical outcome, increased drug concentrations, and reduced immunogenicity. Strategies based on TDM of TNF inhibitors seem promising for RA, but randomized controlled trials are required to support this. A concentration-response relationship may exist with tocilizumab, and immunogenicity seems rare. Finally, the relevance of TDM for RA patients receiving rituximab and abatacept remains unclear.